A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis

Bilal, Jawad; Riaz, Irbaz Bin; Kamal, Muhammad Umar; Elyan, Mazen; Sudano, Dominick; Khan, Muhammad Asim

doi:10.1097/rhu.0000000000000583

Cited by 24 publications

(22 citation statements)

References 33 publications

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“…10 No comparative clinical trials of ixekizumab in the treatment of psoriatic arthritis have been published. Of two systematic reviews, 11,12 one suggested that secukinumab may be superior to other biological agents. 11 However, NICE concluded that ixekizumab is as effective as other biological therapies in this indica-tion.…”

Section: Efficacymentioning

confidence: 99%

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

266

309

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Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

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Section: Efficacymentioning

confidence: 99%

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Sbidian

Chaimani

García‐Doval

et al. 2017

Cochrane Database of Systematic Reviews

266

309

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“…Various safety end points were also evaluated, including treatment-emergent adverse events (TEAEs), serious/severe adverse events (SAEs), discontinuation due to adverse events and all-cause discontinuation. Although recent NMAs have been conducted comparing bDMARDs in PsA,10–14 few include ixekizumab, a recently approved high-affinity monoclonal antibody that selectively targets IL-17A 15. In addition, publication and dissemination of NMA results are essential activities to support international health technology assessments of ixekizumab in PsA.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis

Ruyssen‐Witrand

Perry

Watkins³

et al. 2020

RMD Open

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BackgroundBiologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs are used in patients with psoriatic arthritis (PsA), but few studies directly compare their clinical efficacy. In such situations, network meta-analysis (NMA) can inform evidence-based decision-making.ObjectiveTo evaluate the comparative efficacy and safety of approved bDMARDs in patients with PsA.MethodsBayesian NMA was conducted to compare the clinical efficacy of bDMARDs at weeks 12‒16 in bDMARD-naïve patients with PsA in terms of American College of Rheumatology (ACR) criteria, Psoriatic Arthritis Response Criteria (PsARC) and Psoriasis Area and Severity Index (PASI). Safety end points were evaluated in the overall mixed population of bDMARD-naive and bDMARD-experienced patients.ResultsFor ACR, all treatments except abatacept were statistically superior to placebo. Infliximab was most effective, followed by golimumab and etanercept, which were statistically superior to most other treatments. Ixekizumab 80 mg every 2 weeks (Q2W) was statistically superior to abatacept subcutaneous, apremilast and both regimens of ustekinumab; similar findings were observed for ixekizumab 80 mg Q4W. For PsARC response, ixekizumab did not significantly differ from other therapies, except for golimumab, infliximab and etanercept, which were superior to most other agents including ixekizumab. For PASI response, infliximab was numerically most effective, but was not statistically superior to ixekizumab, which was the next best performing agent. Analysis of safety end points identified few differences between treatments.ConclusionOur NMA confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments.

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“…A systematic review and meta-analysis, being distinct from the individual studies, enables us to describe more comprehensive and accurate data by raising the persuasive power and resolution after synthesizing the outcomes of each analysis. To our knowledge, this study is the first meta-analysis [30,31]. A more recent network meta-analysis using RCT data recruiting 12 types of bDMARDs in psoriatic arthritis found that both secukinumab and ixekizumab are safe and efficacious treatments for active psoriatic arthritis during induction therapy, and further analysis suggested a superiority of secukinumab to ixekizumab in the American College of Rheumatology criteria of ACR20 and a 75% improvement in psoriasis area and severity index (PASI75) [32].…”

Section: Discussionmentioning

confidence: 86%

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

Yin

Wang

Liu

et al. 2020

Preprint

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Objectives: To systematically assess the efficacy and safety of IL-17 inhibitors in patients with active ankylosing spondylitis. Methods: A systematic review of the literature was performed for randomized controlled trials (RCTs) concerning IL-17 inhibitors in patients with ankylosing spondylitis. Meta-analyses were used to determine the efficacy and safety of the IL-17 inhibitors in the treatment of these patients. The primary end point was predefined as the proportion of patients with at least 20% improvement in the Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16, and the secondary end point was defined as ASAS40 at week 16. Results: Six phase III randomized, double-blind, placebo-controlled trials including 1733 patients (1153 patients received IL-17 inhibitors, including secukinumab or ixekizumab, whereas 580 patients received a placebo as comparators) were included. At week 16, the IL-17 inhibitor regimen produced a significant increase in the ASAS20 response rate (RR=1.63, 95% CI 1.45 to 1.84, p=0.00) and the secondary endpoint ASAS40 response rate (RR=2.12, 95% CI 1.75 to 2.56, p=0.00) versus those for the placebo. With respect to the safety profile, more treatment-emergent adverse events (RR=1.11, 95% CI 1.01 to 1.22, p=0.03) and non-severe infections (RR=1.82, 95% CI 1.40 to 2.37, p<0.001) were described after treatment with IL-17 inhibitors than after treatment with placebo, while no increased risk of other adverse events was indicated after IL-17 inhibitor therapy, including death, discontinuation due to adverse events, or serious adverse events. Conclusions: IL-17 inhibitors produced favourable response rates but an increased risk of non-severe infections in the treatment of active ankylosing spondylitis.

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A Systematic Review and Meta-analysis of Efficacy and Safety of Novel Interleukin Inhibitors in the Management of Psoriatic Arthritis

Abstract: Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA.

Cited by 24 publications

References 33 publications

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis

Efficacy and safety of biologics in psoriatic arthritis: a systematic literature review and network meta-analysis

Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis

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